Characterization of Changes in Serum Anti-Glycan Antibodies in Crohn's Disease – a Longitudinal Analysis

INTRODUCTION: Anti-glycan antibodies are a promising tool for differential diagnosis and disease stratification of patients with Crohn's disease (CD). We longitudinally assessed level and status changes of anti-glycan antibodies over time in individual CD patients as well as determinants of this phenomenon. METHODS: 859 serum samples derived from a cohort of 253 inflammatory bowel disease (IBD) patients (207 CD, 46 ulcerative colitis (UC)) were tested for the presence of anti-laminarin (Anti-L), anti-chitin (Anti-C), anti-chitobioside (ACCA), anti-laminaribioside (ALCA), anti-mannobioside (AMCA) and anti-Saccharomyces cerevisiae (gASCA) antibodies by ELISA. All patients had at least two and up to eleven serum samples taken during the disease course. RESULTS: Median follow-up time for CD was 17.4 months (Interquartile range (IQR) 8.0, 31.6 months) and for UC 10.9 months (IQR 4.9, 21.0 months). In a subgroup of CD subjects marked changes in the overall immune response (quartile sum score) and levels of individual markers were observed over time. The marker status (positive versus negative) remained widely stable. Neither clinical phenotype nor NOD2 genotype was associated with the observed fluctuations. In a longitudinal analysis neither changes in disease activity nor CD behavior led to alterations in the levels of the glycan markers. The ability of the panel to discriminate CD from UC or its association with CD phenotypes remained stable during follow-up. In the serum of UC patients neither significant level nor status changes were observed. CONCLUSIONS: While the levels of anti-glycan antibodies fluctuate in a subgroup of CD patients the antibody status is widely stable over time

Acute paranoid psychosis as sole clinical presentation of hepatic artery thrombosis after living donor liver transplantation

<p>Abstract</p> <p>Background</p> <p>Hepatic artery thrombosis is a devastating complication after orthotopic liver transplantation often requiring revascularization or re-transplantation. It is associated with considerably increased morbidity and mortality. Acute cognitive dysfunction such as delirium or acute psychosis may occur after major surgery and may be associated with the advent of surgical complications.</p> <p>Case presentation</p> <p>Here we describe a case of hepatic artery thrombosis after living-donor liver transplantation which was not preceded by signs of liver failure but rather by an episode of acute psychosis. After re-transplantation the patient recovered without sequelae.</p> <p>Conclusion</p> <p>This case highlights the need to remain cautious when psychiatric disorders occur in patients after liver transplantation. The diagnostic procedures should not be restricted to medical or neurological causes of psychosis alone but should also focus vascular complications related to orthotopic liver transplantation.</p

Effects of Screening and Brief Intervention Training on Resident and Faculty Alcohol Intervention Behaviours: A Pre- Post-Intervention Assessment

Background: Many hazardous and harmful drinkers do not receive clinician advice to reduce their drinking. Previous studies suggest under-detection and clinician reluctance to intervene despite awareness of problem drinking (PD). The Healthy Habits Project previously reported chart review data documenting increased screening and intervention with hazardous and harmful drinkers after training clinicians and implementing routine screening. This report describes the impact of the Healthy Habits training program on clinicians\u27 rates of identification of PD, level of certainty in identifying PD and the proportion of patients given advice to reduce alcohol use, based on self-report data using clinician exit questionnaires. Methods: 28 residents and 10 faculty in a family medicine residency clinic completed four cycles of clinician exit interview questionnaires before and after screening and intervention training. Rates of identifying PD, level of diagnostic certainty, and frequency of advice to reduce drinking were compared across intervention status (pre vs. post). Findings were compared with rates of PD and advice to reduce drinking documented on chart review. Results: 1,052 clinician exit questionnaires were collected. There were no significant differences in rates of PD identified before and after intervention (9.8% vs. 7.4%, p = .308). Faculty demonstrated greater certainty in PD diagnoses than residents (p = .028) and gave more advice to reduce drinking (p = .042) throughout the program. Faculty and residents reported higher levels of diagnostic certainty after training (p = .039 and .030, respectively). After training, residents showed greater increases than faculty in the percentage of patients given advice to reduce drinking (p = .038), and patients felt to be problem drinkers were significantly more likely to receive advice to reduce drinking by all clinicians (50% vs. 75%, p = .047). The number of patients receiving advice to reduce drinking after program implementation exceeded the number of patients felt to be problem drinkers. Recognition rates of PD were four to eight times higher than rates documented on chart review (p = .028). Conclusion: This program resulted in greater clinician certainty in diagnosing PD and increases in the number of patients with PD who received advice to reduce drinking. Future programs should include booster training sessions and emphasize documentation of PD and brief intervention

Clostridium difficile 027 infection in Central Italy

Background Clostridium difficile (CD) has increasingly become recognised as a significant international health burden, often associated with the healthcare environment. The upsurge in incidence of CD coincided with the emergence of a hypervirulent strain of CD characterized as 027. In 2010, 8 cases of CD 027 infections were identified in Italy. Since then, no further reports have been published. We describe 10 new cases of CD 027 infection occurring in Italy. Methods Since December 2010, stool samples of patients with severe diarrhea and clinical suspicion of the presence of a hypervirulent strain, were tested for CD 027 by the Xpert C. difficile PCR assay (Cepheid, Sunnyvale, CA). Clinical, epidemiological and laboratory data were collected. Results From December 2010 to April 2012, 24 faecal samples from 19 patients who fit the above criteria were submitted to our laboratory. Samples were collected from 7 different hospitals. Of these, 17 had a positive PCR for CD and 10 were the epidemic 027 strain (59%). All PCR positive samples had a positive EIA toxin A/B test. Nine of 10 patients were recently exposed to antimicrobials and were healthcare-associated, including 4 with a history of long term care facility (LTCF) admission; the remaining case was community-associated, namely the wife of a patient with hospital-acquired CD 027 infection. Five patients experienced at least one recurrence of CD associated diarrhea (CDAD) with a total of 12 relapsing episodes. Of these, two patients had 5 and 6 relapses respectively. We compared the 10 patients with 027 CDAD versus the 7 patients with non-027 CDAD. None of the 7 patients with non-027 CDAD had a recent history of LTCF admission and no subsequent relapses were observed (p = 0.04). Conclusions Our study shows that CD 027 is emerging in healthcare facilities in Italy. Whilst nosocomial acquisition accounted for the majority of such cases, 4 patients had history of a recent stay in a LTCF. We highlight the substantial risks of this highly transmissible organism in such environments. Moreover, 50% of our patients with CDAD from the 027 strain had high relapse rates which may serve to further establish this strain within the Italian health and social care systems

Infliximab Induces Clonal Expansion of γδ-T Cells in Crohn's Disease: A Predictor of Lymphoma Risk?

BACKGROUND: Concominant with the widespread use of combined immunotherapy in the management of Crohn's disease (CD), the incidence of hepato-splenic gamma-delta (γδ)-T cell lymphoma has increased sharply in CD patients. Malignant transformation of lymphocytes is believed to be a multistep process resulting in the selection of malignant γδ-T cell clones. We hypothesised that repeated infusion of anti-TNF-α agents may induce clonal selection and that concurrent treatment with immunomodulators further predisposes patients to γδ-T cell expansion. METHODOLOGY/PRINCIPAL FINDINGS: We investigated dynamic changes in the γδ-T cells of patient with CD following treatment with infliximab (Remicade®; n=20) or adalimumab (Humira®; n=26) using flow cytometry. In patients with a high γδ-T cell level, the γδ-T cells were assessed for clonality. Of these 46 CD patients, 35 had a γδ-T cells level (mean 1.6%) comparable to healthy individuals (mean 2.2%), and 11 CD patients (24%) exhibited an increased level of γδ-T cells (5-15%). In the 18 patients also receiving thiopurines or methotrexate, the average baseline γδ-T cell level was 4.4%. In three male CD patients with a high baseline value, the γδ-T cell population increased dramatically following infliximab therapy. A fourth male patient also on infliximab monotherapy presented with 20% γδ-T cells, which increased to 25% shortly after treatment and was 36% between infusions. Clonality studies revealed an oligoclonal γδ-T cell pattern with dominant γδ-T cell clones. In support of our clinical findings, in vitro experiments showed a dose-dependent proliferative effect of anti-TNF-α agents on γδ-T cells. CONCLUSION/SIGNIFICANCE: CD patients treated with immunomodulators had constitutively high levels of γδ-T cells. Infliximab exacerbated clonal γδ-T cell expansion in vivo and induced γδ-T cell proliferation in vitro. Overall, young, male CD patients with high baseline γδ-T cell levels may be at an increased risk of developing malignant γδ-T cell lymphomas following treatment with anti-TNF-α agents

Frequency and Nature of Incidental Extra-Enteric Lesions Found on Magnetic Resonance Enterography (MR-E) in Patients with Inflammatory Bowel Diseases (IBD)

The aim of this study was to determine the occurrence of extra-enteric findings in a large cohort of patients undergoing magnetic resonance enterography (MR-E) and to classify the clinical significance of these findings.We retrospectively analyzed 1154 MR-E performed in 1006 patients referred to our radiological department between 1999-2005. The reasons for referral were suspected or proven inflammatory bowel diseases (IBD) (n = 710), further diagnostic work-up for small bowel disease because of non-specific abdominal symptoms (SBD; n = 182) or suspected small bowel malignancies (SBM; n = 114). All extra-enteric findings were reviewed by a radiologist and a gastroenterologist and were classified as having high, moderate, or low significance for further diagnostic or therapeutic procedures.The average age of all patients was 40+/-16 (Mean+/-SD) years (y) (IBD 35+/-13 y; SBD 49+/-16 y; SBM 57+/-15 y). A total of 1113 extra-enteric findings were detected in 600 of 1006 patients (59.6%). Of these findings 180 (16.2%) were judged as having a high, 212 (19.0%) a moderate and 721 (64.8%) a low significance. On a per group basis in patients with IBD 12.0% of the findings were of major clinical significance compared to 13.7% and 33.3% in patients with SBD and SBM, respectively. The most common major findings were abscesses (69.9%) in the IBD group and extraintestinal tumors, metastases or masses in the SBD and SBM groups (41.9% and 74.2%, respectively).MR-E reveals a substantial number of extra-enteric findings, supporting the role of a cross-sectional imaging method for the evaluation of the small bowel

Measurement and interpretation of same-sign W boson pair production in association with two jets in pp collisions at s = 13 TeV with the ATLAS detector

This paper presents the measurement of fducial and diferential cross sections for both the inclusive and electroweak production of a same-sign W-boson pair in association with two jets (W±W±jj) using 139 fb−1 of proton-proton collision data recorded at a centre-of-mass energy of √s = 13 TeV by the ATLAS detector at the Large Hadron Collider. The analysis is performed by selecting two same-charge leptons, electron or muon, and at least two jets with large invariant mass and a large rapidity diference. The measured fducial cross sections for electroweak and inclusive W±W±jj production are 2.92 ± 0.22 (stat.) ± 0.19 (syst.)fb and 3.38±0.22 (stat.)±0.19 (syst.)fb, respectively, in agreement with Standard Model predictions. The measurements are used to constrain anomalous quartic gauge couplings by extracting 95% confdence level intervals on dimension-8 operators. A search for doubly charged Higgs bosons H±± that are produced in vector-boson fusion processes and decay into a same-sign W boson pair is performed. The largest deviation from the Standard Model occurs for an H±± mass near 450 GeV, with a global signifcance of 2.5 standard deviations

Combination of searches for heavy spin-1 resonances using 139 fb−1 of proton-proton collision data at s = 13 TeV with the ATLAS detector

A combination of searches for new heavy spin-1 resonances decaying into different pairings of W, Z, or Higgs bosons, as well as directly into leptons or quarks, is presented. The data sample used corresponds to 139 fb−1 of proton-proton collisions at = 13 TeV collected during 2015–2018 with the ATLAS detector at the CERN Large Hadron Collider. Analyses selecting quark pairs (qq, bb, , and tb) or third-generation leptons (τν and ττ) are included in this kind of combination for the first time. A simplified model predicting a spin-1 heavy vector-boson triplet is used. Cross-section limits are set at the 95% confidence level and are compared with predictions for the benchmark model. These limits are also expressed in terms of constraints on couplings of the heavy vector-boson triplet to quarks, leptons, and the Higgs boson. The complementarity of the various analyses increases the sensitivity to new physics, and the resulting constraints are stronger than those from any individual analysis considered. The data exclude a heavy vector-boson triplet with mass below 5.8 TeV in a weakly coupled scenario, below 4.4 TeV in a strongly coupled scenario, and up to 1.5 TeV in the case of production via vector-boson fusion